gms | German Medical Science

Background: High dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) carries risks of infectious morbidity. Little is known, however, about the occurrence of invasive fungal diseases (IFDs) in pediatric patients undergoing autologous HSCT.

Patients and methods: In a retrospective single center study, epidemiology and management burden associated with IFDs were analyzed in all patients who underwent autologous HSCT for solid tumors or lymphoma between 2005 and 2015. Clinical, radiographic, and microbiological data were assessed until engraftment and up to 100 days post-transplant. The primary endpoint was the incidence of proven, probable, and possible IFDs according to current EORTC/MSG definitions. Interventions for persistent or recurrent fever consisted of pulmonary computed tomography (CT) imaging and appropriate modification of antibacterial empiric therapy. The use of systemic antifungal prophylaxis and of empiric antifungal therapy were at the discretion of the respective attending physician.

Results: During the ten-year observation period, 95 patients underwent 103 autologous HSCT procedures (solid tumors 92, lymphoma 11; mean age 9.9, range 0.75-20). High-dose chemotherapy included treosulfan plus melphalan (50), carboplatin based (33), and various other (20) regimens. The mean time to neutrophil engraftment and to discharge were 12 (r, 7-29) and 16 (r, 11-72) days, respectively. Systemic antifungal prophylaxis was administered to 49 HSCT procedures (47.5%) and consisted mostly (43) of fluconazole. At least one CT scan was performed in 21 procedures. There was no single case of invasive yeast infection. Similarly, no single case of proven/probable mold infection was diagnosed. Nine cases (8.7%) fulfilled criteria of a possible pulmonary mold infection during neutropenia and received mold active antifungal therapy for a median of 14 days (r, 7-35). In an additional 12 procedures, empiric antifungal therapy with mold active agents was given for a median of 8 days (r, 3-105). Considering the total antifungal treatment burden of the cohort, systemic antifungal treatment was administered in 63 procedures (61.2%), either as systemic prophylaxis only (42; 40,8%), prophylaxis followed by empirical or directed treatment (7; 6.8%) and empirical or directed treatment only (14; 13.6%). Grades III/IV mucositis was recorded in 51 procedures and microbiologically documented non-fungal infections in 17. Five patients were transferred to the ICU. One patient died from biopsy documented toxic endothelial damage at day 83 post-transplant, accounting for an overall mortality rate of <1%.

Conclusions: Autologous HSCT for solid tumors or lymphoma was associated with low morbidity from IFDs at our institution. However, utilization of pulmonary CT imaging and use of systemic antifungal agents for prevention and management of suspected IFDs were considerable.